Genetic studies have shown that human T-ALLs can be divided into subgroups that are characterized by unique gene expression signatures and relate to stages of T-cell differentiation at which the leukemic cells arrest. Each molecular subgroup has characteristic genetic abnormalities that cause aberrant activation of specific T-ALL transcription factor oncogenes, including LYL1/MEF2C, HOXA, TLX1, TLX3 and TAL1/LMO2. Notably, the recently described Early T-cell Precursor ALL (ETP-ALL) patients have leukemic cells that show an early block in T-cell differentiation and significantly overlap with LYL1-positive T-ALL and MEF2C-dysregulated immature T-ALL. We studied the gene expression profiles of 64 primary T-ALL samples and found a high BCL-2 expression in immature T-ALL patients compared to patients belonging to other subgroups.
ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia.
Specimen part
View SamplesDrought is an important environmental factor affecting plant growth and biomass production. Despite this importance little is known on the molecular mechanisms regulating plant growth under water limiting conditions. The main goal of this work was to investigate, using a combination of growth and molecular profiling techniques, how stress arrests CELl proliferation in Arabidopsis thaliana leaves upon osmotic stress imposition.
Pause-and-stop: the effects of osmotic stress on cell proliferation during early leaf development in Arabidopsis and a role for ethylene signaling in cell cycle arrest.
Specimen part
View SamplesDrought is an important environmental factor affecting plant growth and biomass production. Despite this importance, little is known on the molecular mechanisms regulating plant growth under water limiting conditions. The main goal of this work was to investigate, using a combination of growth and molecular profiling techniques, how Arabidopsis thaliana leaves adapt their growth to prolonged mild osmotic stress. Fully proliferating, expanding and mature leaves were harvested from plants grown on plates without (control) or with 25mM mannitol (osmotic stress) and compared to seedlings at stage 1.03.
Developmental stage specificity and the role of mitochondrial metabolism in the response of Arabidopsis leaves to prolonged mild osmotic stress.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide promoter methylation analysis in neuroblastoma identifies prognostic methylation biomarkers.
Treatment
View Samples8 neuroblastoma (NB) cell lines (CLB-GA, IMR-32, SH-SY5Y, N206, CHP-902R, LAN-2, SK-N-AS, SJNB-1) were profiled on the Affymetrix HGU-133plus2,0 platform before and after treatment with DAC (2'-deoxy-5-azacytidine) to investigate the influence on expression after inhibiting DNA-methylation
Genome-wide promoter methylation analysis in neuroblastoma identifies prognostic methylation biomarkers.
Treatment
View SamplesTargeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the nature and dynamics of immune cells in the lung cancer micro-environment. Dendritic cells (DCs) represent a heterogenous and highly plastic immune cell system with a central role in controlling immune responses. The intratumoral infiltration and activation status of DCs emerge as clinically relevant parameters in lung cancer. In this study we used an orthotopic preclinical model of lung cancer to interrogate the transcriptome of lung tumor-infiltrating DCs and extract novel biologically and clinically relevant information. Lung tumor-infiltrating leukocytes expressing generic DC markers were found to predominantly consist of CD11b+ cells which, compared to peritumoral lung DC counterparts, strongly over-express the T cell inhibitory molecule PD-L1 and acquire classic markers of tumor-supporting macrophages (TAM) on their surface. Transcriptome analysis of these CD11b+ tumor-infiltrating DCs (TIDCs) indicates impaired anti-tumoral immunogenicity, confirms the skewing towards TAM-related features, and indicates exposure to a hypoxic environment. In paralled, TIDCs display a specific micro-RNA signature dominated by the prototypical lung cancer oncomir miR-31. Hypoxia was found to drive intrinsic miR-31 expression in CD11b+DCs. Conditioned medium of mir-31-overexpressing CD11b+DCs induces pro-invasive lung cancer cell shape changes and is enriched with the pro-metastatic factors S100A8 and S100A9. Finally, analysis of TCGA datasets reveals that the TIDC-associated miRNA signature has a negative prognostic impact in non-small cell lung cancer. Together, these data suggest a novel mechanism through which lung cancer co-opts the plasticity of the DC system to support tumoral progression. Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the nature and dynamics of immune cells in the lung cancer micro-environment. Dendritic cells (DCs) represent a heterogenous and highly plastic immune cell system with a central role in controlling immune responses. The intratumoral infiltration and activation status of DCs emerge as clinically relevant parameters in lung cancer. In this study we used an orthotopic preclinical model of lung cancer to interrogate the transcriptome of lung tumor-infiltrating DCs and extract novel biologically and clinically relevant information. Lung tumor-infiltrating leukocytes expressing generic DC markers were found to predominantly consist of CD11b+ cells which, compared to peritumoral lung DC counterparts, strongly over-express the T cell inhibitory molecule PD-L1 and acquire classic markers of tumor-supporting macrophages (TAM) on their surface. Transcriptome analysis of these CD11b+ tumor-infiltrating DCs (TIDCs) indicates impaired anti-tumoral immunogenicity, confirms the skewing towards TAM-related features, and indicates exposure to a hypoxic environment. In paralled, TIDCs display a specific micro-RNA signature dominated by the prototypical lung cancer oncomir miR-31. Hypoxia was found to drive intrinsic miR-31 expression in CD11b+DCs. Conditioned medium of mir-31-overexpressing CD11b+DCs induces pro-invasive lung cancer cell shape changes and is enriched with the pro-metastatic factors S100A8 and S100A9. Finally, analysis of TCGA datasets reveals that the TIDC-associated miRNA signature has a negative prognostic impact in non-small cell lung cancer. Together, these data suggest a novel mechanism through which lung cancer co-opts the plasticity of the DC system to support tumoral progression.
The transcriptome of lung tumor-infiltrating dendritic cells reveals a tumor-supporting phenotype and a microRNA signature with negative impact on clinical outcome.
Specimen part
View SamplesCharacterization of intraepithelial ILC on the basis of CD8 and Ly49E expression
A Murine Intestinal Intraepithelial NKp46-Negative Innate Lymphoid Cell Population Characterized by Group 1 Properties.
Specimen part
View SamplesHydrogen peroxide (H2O2) can act as a signaling molecule that influences various aspects of plant growth and development, including stress signaling and cell death. Catalase deficient plants are pioneering systems which accumulate hydrogen peroxide (H2O2) from peroxisomal origin during photorespiratory challenges. Respiratory burst oxidase homologues D and F are known to participate in intracellular oxidative stress response launched in cat2 mutants (Chaouch et al., 2012). We studied the compared the transcriptional response of cat2 rbohD and cat2 rbohF double mutants versus the cat2 background to further adress their role during photorespiratory stress.
The ROS Wheel: Refining ROS Transcriptional Footprints.
Age
View SamplesOsteoarthritic cartilage has largely been investigated, however supporting structures as the acetabular labrum are less investigated. In this studies we aimed to identify differences in gene expression between healthy and osteoarthritic labrum cells
Distinct dysregulation of the small leucine-rich repeat protein family in osteoarthritic acetabular labrum compared to articular cartilage.
Specimen part, Subject
View SamplesSix weeks old Arabidopsis plants were transferred to a low CO2 (100 ppm) environment during 24 hours and compared to control plants kept under ambient CO2 conditions. Limited CO2 availability will cause higher rates of photorespiration and affect the plant redox homeostasis. We studied the transcriptomic impact of exposing plants to a lower CO2 environment to further eliculidate the signaling pathways during photorespiratory stress.
The ROS Wheel: Refining ROS Transcriptional Footprints.
Age, Treatment
View Samples